rs1467912

Positions:

• chr6-36285433-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001374623.1(PNPLA1):​c.206-5887T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 152,080 control chromosomes in the GnomAD database, including 31,677 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.65 (31677 hom., cov: 32)
• Consequence: PNPLA1 NM_001374623.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.575

Genes affected

PNPLA1 (HGNC:21246): (patatin like phospholipase domain containing 1) The protein encoded by this gene belongs to the patatin-like phospholipase (PNPLA) family, which is characterized by the presence of a highly conserved patatin domain. PNPLA family members have diverse lipolytic and acyltransferase activities, and are key elements in lipid metabolism. While other members of this family have been well characterized, the function of this gene remained an enigma. However, recent studies show that this gene is expressed in the skin epidermal keratinocytes, and has a role in glycerophospholipid metabolism in the cutaneous barrier. Consistent with these observations, mutations in this gene are associated with ichthyosis in human (autosomal recessive congenital ichthyoses, ARCI) and dog. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNPLA1	NM_001374623.1	c.206-5887T>C		intron_variant		ENST00000636260.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNPLA1	ENST00000636260.2	c.206-5887T>C		intron_variant		5	NM_001374623.1	A2

Frequencies

GnomAD3 genomes AF: 0.645 AC: 98046 AN: 151960 Hom.: 31650 Cov.: 32

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.645

Gnomad OTH AF: 0.697

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.645 AC: 98118 AN: 152080 Hom.: 31677 Cov.: 32 AF XY: 0.641 AC XY: 47670 AN XY: 74382

Gnomad4 AFR AF: 0.659

Gnomad4 AMR AF: 0.680

Gnomad4 ASJ AF: 0.674

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.589

Gnomad4 NFE AF: 0.645

Gnomad4 OTH AF: 0.701

Alfa AF: 0.642 Hom.: 4452

Bravo AF: 0.657

Asia WGS AF: 0.656 AC: 2282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	10
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1467912; hg19: chr6-36253210; COSMIC: COSV57234356;